Kleiber Niina, Tromp Krista, Mooij Miriam G, van de Vathorst Suzanne, Tibboel Dick, de Wildt Saskia N
Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, P.O. Box 2060, 3000 CB, Rotterdam, The Netherlands.
Paediatr Drugs. 2015 Feb;17(1):43-53. doi: 10.1007/s40272-014-0101-5.
Critical illness and treatment modalities change pharmacokinetics and pharmacodynamics of medications used in critically ill children, in addition to age-related changes in drug disposition and effect. Hence, to ensure effective and safe drug therapy, research in this population is urgently needed. However, conducting research in the vulnerable population of the pediatric intensive care unit (PICU) presents with ethical challenges. This article addresses the main ethical issues specific to drug research in these critically ill children and proposes several solutions. The extraordinary environment of the PICU raises specific challenges to the design and conduct of research. The need for proxy consent of parents (or legal guardians) and the stress-inducing physical environment may threaten informed consent. The informed consent process is challenging because emergency research reduces or even eliminates the time to seek consent. Moreover, parental anxiety may impede adequate understanding and generate misconceptions. Alternative forms of consent have been developed taking into account the unpredictable reality of the acute critical care environment. As with any research in children, the burden and risk should be minimized. Recent developments in sample collection and analysis as well as pharmacokinetic analysis should be considered in the design of studies. Despite the difficulties inherent to drug research in critically ill children, methods are available to conduct ethically sound research resulting in relevant and generalizable data. This should motivate the PICU community to commit to drug research to ultimately provide the right drug at the right dose for every individual child.
危重病及治疗方式会改变危重症儿童所用药物的药代动力学和药效学，此外还会改变与年龄相关的药物处置和效应。因此，为确保有效且安全的药物治疗，迫切需要针对这一人群开展研究。然而，在儿科重症监护病房（PICU）这一脆弱人群中开展研究存在伦理挑战。本文探讨了这些危重症儿童药物研究特有的主要伦理问题，并提出了几种解决方案。PICU的特殊环境给研究的设计和实施带来了特殊挑战。需要父母（或法定监护人）的代理同意以及压力较大的身体环境可能会威胁到知情同意。知情同意过程具有挑战性，因为紧急研究减少甚至消除了寻求同意的时间。此外，父母的焦虑可能会妨碍充分理解并产生误解。考虑到急性重症监护环境的不可预测性，已开发出替代形式的同意。与任何儿童研究一样，应将负担和风险降至最低。在研究设计中应考虑样本采集与分析以及药代动力学分析的最新进展。尽管危重症儿童药物研究存在固有困难，但仍有方法可开展符合伦理规范的研究，从而得出相关且具有普遍性的数据。这应促使PICU群体致力于药物研究，最终为每个儿童提供正确剂量的正确药物。
